Sozzani S, Allavena P, D'Amico G, Luini W, Bianchi G, Kataura M, Imai T, Yoshie O, Bonecchi R, Mantovani A
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Immunol. 1998 Aug 1;161(3):1083-6.
Upon exposure to immune or inflammatory stimuli, dendritic cells (DC) migrate from peripheral tissues to lymphoid organs, where they present Ag. CC chemokines induce chemotactic and transendothelial migration of immature DC, in vitro. Maturation of DC by CD40L, or by LPS, IL-1, and TNF, induces down-regulation of the two main CC chemokine receptors expressed by these cells, CCR1 and CCRS, and abrogates chemotaxis to their ligands. Inhibition was rapid (<1 h) and included the unrelated agent FMLP. Concomitantly, the expression of CCR7 and the migration to its ligand EBI1 ligand chemokine (ELC)/macrophage inflammatory protein (MIP)-3beta, a chemokine expressed in lymphoid organs, were strongly up-regulated, though with slower kinetics (24-48 h). Rapid inhibition of responsiveness to chemoattractants present at sites of inflammation and immune reaction may be permissive for leaving peripheral tissues. Conversely, the slower acquisition of responsiveness to ELC/MIP-3beta may guide subsequent localization of DC in lymphoid organs.
在受到免疫或炎症刺激后，树突状细胞（DC）从外周组织迁移至淋巴器官，并在那里呈递抗原。CC趋化因子在体外可诱导未成熟DC发生趋化性迁移和跨内皮迁移。通过CD40L或脂多糖、白细胞介素-1及肿瘤坏死因子使DC成熟，可导致这些细胞表达的两种主要CC趋化因子受体CCR1和CCR5下调，并消除对其配体的趋化作用。抑制作用迅速（<1小时），且包括无关因子N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）。同时，CCR7的表达以及对其配体EBI1配体趋化因子（ELC）/巨噬细胞炎性蛋白（MIP）-3β（一种在淋巴器官中表达的趋化因子）的迁移能力均显著上调，不过动力学变化较慢（24 - 48小时）。对炎症和免疫反应部位存在的趋化因子反应性的快速抑制可能有利于离开外周组织。相反，对ELC/MIP - 3β反应性的较慢获得可能会引导DC随后在淋巴器官中的定位。
